tbuckley/cabot-search huggingface dataset:
Quantitative Sensory Testing to Characterize Sensory Changes in Hidradenitis Suppurativa Skin Lesions
Authors: Ali Alsouhibani, Patrick Speck, Emily F. Cole, Danielle E. Mustin, Yiwen Li, Jason R. Barron, Lauren A. V. Orenstein, Daniel E. Harper
Journal: JAMA Dermatology (2023)

Pain is the most impactful symptom in patients with hidradenitis suppurativa (HS). Characterization of sensory profiles may improve understanding of pain mechanisms in HS and facilitate identification of effective pain management strategies.
AACR Cancer Centers Alliance: Fostering Collaboration and Innovation to Advance Lifesaving Scientific Discoveries for Patients
Authors: Carlos L. Arteaga, John L. Cleveland, Margaret Foti, Ruben A. Mesa, Louis M. Weiner, Cheryl L. Willman, David A. Tuveson
Journal: Cancer Discovery (2023)

Basic and clinical cancer research discoveries stemming from the nation's cancer centers have markedly improved outcomes for many cancer patients. Despite this forward momentum in our progress against this complex disease, cancer in all its forms remains a major public health challenge that touches the lives of nearly every American, either directly or indirectly. The newly formed AACR Cancer Centers Alliance will accelerate the pace of discovery by providing an ongoing mechanism for transferring new knowledge, sharing resources, developing national demonstration projects, and driving innovation that impacts cancer science, cancer care delivery, and science and health policy.
Cutaneous Vascular Malformations in a 53-Year-Old Woman With Neurologic Symptoms
Authors: Jonas Rauterberg, Julia Schreml, Iliana Tantcheva-Poór
Journal: JAMA Dermatology (2023)

A woman in her 50s presented with bluish, keratotic papules and nodules on the lower legs and lipolymphedema of the lower legs. What is your diagnosis?
Skin-Related Quality of Life During Autoimmune Bullous Disease Course
Authors: Zachary H. Hopkins, Amber Jimenez, Vanina L. Taliercio, Jennie T. Clarke, Christopher B. Hansen, Christopher M. Hull, Jamie L. W. Rhoads, John J. Zone, Vikram N. Sahni, Jacob Kean, Aaron M. Secrest
Journal: JAMA Dermatology (2023)

Autoimmune bullous diseases (AIBDs) are chronic relapsing-remitting conditions with significant morbidity. Skin-related quality of life (SRQL) may vary by AIBD subtype and disease type. Disease severity and flare severity can be difficult to define; SRQL can offer a key insight.
Natural human Bet v 1‐specific IgG antibodies recognize non‐conformational epitopes whereas IgE reacts with conformational epitopes
Authors: Georgii Brazhnikov, Evgenii Smolnikov, Alla Litovkina, Tianchi Jiang, Artem Shatilov, Inna Tulaeva, Mikhail Tulaev, Alexander Karaulov, Alina Poroshina, Yury Zhernov, Margarete Focke‐Tejkl, Milena Weber, Oluwatoyin Akinfenwa, Olga Elisyutina, Sergey Andreev, Igor Shilovskiy, Nadezhda Shershakova, Valeriy Smirnov, Elena Fedenko, Tatiana Sergeevna Lepeshkova, Evgeny Cronidovich Beltyukov, Veronika Victorovna Naumova, Michael Kundi, Musa Khaitov, Ursula Wiedermann, Rudolf Valenta, Raffaela Campana
Journal: Allergy (2023)

Abstract Background The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen‐exposed but non‐sensitized subjects has not been studied in detail. Objective To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1‐specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1‐induced basophil activation. Methods Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non‐allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG 1 and IgG 4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N‐terminal (F1) and C‐terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro‐array analysis. The ability of Bet v 1‐specific serum antibodies from non‐allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1‐derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non‐allergic subjects to modulate Bet v 1‐induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients. Results IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG 1 and IgG 4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen‐containing food. Natural Bet v 1‐specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1‐specific basophil activation. Conclusion IgE and IgG antibodies from BPA patients and birch pollen‐exposed non‐sensitized subjects recognize different epitopes. These findings explain why natural allergen‐specific IgG do not protect against allergic symptoms and suggest that allergen‐specific IgE and IgG have different clonal origin.
Eosinophils—from cradle to grave
Authors: Milos Jesenak, Zuzana Diamant, Dagmar Simon, Ellen Tufvesson, Sven F. Seys, Manali Mukherjee, Paige Lacy, Susanne Vijverberg, Tomas Slisz, Anna Sediva, Hans‐Uwe Simon, Ilja Striz, Jana Plevkova, Jurgen Schwarze, Radovan Kosturiak, Neil E. Alexis, Eva Untersmayr, Martina Koziar Vasakova, Edward Knol, Leo Koenderman
Journal: Allergy (2023)

Abstract Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.
HHS Announces First 10 Drugs Up for Price Negotiation
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abortions Increased Among Out-of-State Residents in Massachusetts
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Distinctive patterns of sulfide- and butyrate-metabolizing bacteria after bariatric surgery: potential implications for colorectal cancer risk
Authors: Hisham Hussan, Steven K. Clinton, Elizabeth M. Grainger, Maxine Webb, Cankun Wang, Amy Webb, Bradley Needleman, Sabrena Noria, Jiangjiang Zhu, Fouad Choueiry, Maciej Pietrzak, Michael T. Bailey
Journal: Gut Microbes (2023)

Despite improved cardiometabolic outcomes following bariatric surgery, its long-term impact on colorectal cancer (CRC) risk remains uncertain. In parallel, the influence of bariatric surgery on the host microbiome and relationships with disease outcomes is beginning to be appreciated. Therefore, we investigated the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on the patterns of sulfide-reducing and butyrate-producing bacteria, which are hypothesized to modulate CRC risk after bariatric surgery. In this single-center, cross-sectional study, we included 15 pre-surgery subjects with severe obesity and patients who are at a median (range) of 25.6 (9.9–46.5) months after RYGB (n = 16) or VSG (n = 10). The DNA abundance of fecal bacteria and enzymes involved in butyrate and sulfide metabolism were identified using metagenomic sequencing. Differences between pre-surgery and post-RYGB or post-VSG cohorts were quantified using the linear discriminant analysis (LDA) effect size (LEfSe) method. Our sample was predominantly female (87%) with a median (range) age of 46 (23–71) years. Post-RYGB and post-VSG patients had a higher DNA abundance of fecal sulfide-reducing bacteria than pre-surgery controls (LDA = 1.3–4.4, p < .05). The most significant enrichments were for fecal E. coli, Acidaminococcus and A. finegoldii after RYGB, and for A. finegoldii, S. vestibularis, V. parvula after VSG. As for butyrate-producing bacteria, R. faecis was more abundant, whereas B. dentium and A. hardus were lower post-RYGB vs. pre-surgery. B. dentium was also lower in post-VSG vs. pre-surgery. Consistent with these findings, our analysis showed a greater enrichment of sulfide-reducing enzymes after bariatric surgery, especially RYGB, vs. pre-surgery. The DNA abundance of butyrate-producing enzymes was lower post-RYGB. In conclusion, the two most used bariatric surgeries, RYGB and VSG, are associated with microbiome patterns that are potentially implicated in CRC risk. Future studies are needed to validate and understand the impact of these microbiome changes on CRC risk after bariatric surgery.
Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study
Authors: Ana K. Rosen Vollmar, Nicholas J.W. Rattray, Yuping Cai, Abhishek Jain, Hong Yan, Nicole C. Deziel, Antonia M. Calafat, Allen J. Wilcox, Anne Marie Z. Jukic, Caroline H. Johnson
Journal: Environmental Health Perspectives (2023)

Background: Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function. Objectives: This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility. Methods: Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data. Results: Seven metabolites were associated with paraben concentration (variable importance to projection score >1, false discovery rate–corrected q-value<0.1). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations. Discussion: This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125
Stem Cell Gene Editing Improved Sickle Cell Disease Outcomes
Authors: Emily Harris
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma
Authors: Karen L. Burger, Mario R. Fernandez, Mark B. Meads, Praneeth Sudalagunta, Paula S. Oliveira, Rafael Renatino Canevarolo, Raghunandan Reddy Alugubelli, Alexandre Tungsevik, Gabe De Avila, Maria Silva, Allison I. Graeter, Hongyue A. Dai, Nicole D. Vincelette, Antony Prabhu, Dario Magaletti, Chunying Yang, Weimin Li, Amit Kulkarni, Oliver Hampton, John M. Koomen, William R. Roush, Andrii Monastyrskyi, Anders E. Berglund, Ariosto S. Silva, John L. Cleveland, Kenneth H. Shain
Journal: Cancer Research (2023)

Multiple myeloma remains an incurable malignancy due to acquisition of intrinsic programs that drive therapy resistance. Here we report that casein kinase-1δ (CK1δ) and CK1ε are therapeutic targets in multiple myeloma that are necessary to sustain mitochondrial metabolism. Specifically, the dual CK1δ/CK1ε inhibitor SR-3029 had potent in vivo and ex vivo anti-multiple myeloma activity, including against primary multiple myeloma patient specimens. RNA sequencing (RNA-seq) and metabolic analyses revealed inhibiting CK1δ/CK1ε disables multiple myeloma metabolism by suppressing genes involved in oxidative phosphorylation (OxPhos), reducing citric acid cycle intermediates, and suppressing complexes I and IV of the electron transport chain. Finally, sensitivity of multiple myeloma patient specimens to SR-3029 correlated with elevated expression of mitochondrial genes, and RNA-seq from 687 multiple myeloma patient samples revealed that increased CSNK1D, CSNK1E, and OxPhos genes correlate with disease progression and inferior outcomes. Thus, increases in mitochondrial metabolism are a hallmark of multiple myeloma progression that can be disabled by targeting CK1δ/CK1ε.
Longer-Term Efficacy and Safety of Evinacumab in Patients With Refractory Hypercholesterolemia
Authors: Robert S. Rosenson, Lesley J. Burgess, Christoph F. Ebenbichler, Seth J. Baum, Erik S. G. Stroes, Shazia Ali, Nagwa Khilla, Jennifer McGinniss, Daniel Gaudet, Robert Pordy
Journal: JAMA Cardiology (2023)

Patients with refractory hypercholesterolemia who do not achieve their guideline-defined low-density lipoprotein cholesterol (LDL-C) thresholds despite treatment with maximally tolerated combinations of lipid-lowering therapies (LLTs) have an increased risk of atherosclerotic cardiovascular disease (ASCVD).To evaluate longer-term efficacy and safety of evinacumab in patients with refractory hypercholesterolemia.This randomized clinical trial included a 2-week screening period followed by a 16-week double-blind treatment period (DBTP) for subcutaneous regimens (evinacumab, 450 mg, once weekly [QW]; evinacumab, 300 mg, QW; evinacumab, 300 mg, every 2 weeks; or placebo QW) or a 24-week DBTP for intravenous regimens (evinacumab, 15 mg/kg, every 4 weeks [Q4W]; evinacumab, 5 mg/kg, Q4W; or placebo Q4W); a 48-week open-label treatment period (OLTP) for intravenous treatment only; and a 24-week follow-up period. Patients from 85 sites across 20 countries were recruited for the study; patients with primary hypercholesterolemia (defined as heterozygous familial hypercholesterolemia or established clinical ASCVD without familial hypercholesterolemia) who entered the 48-week OLTP were included. In addition, the patients' hypercholesterolemia was refractory to maximally tolerated LLTs.All patients entering the OLTP received evinacumab, 15 mg/kg, intravenously Q4W.Efficacy outcomes included change in LDL-C level and other lipid/lipoprotein parameters from baseline to week 72 (end of the OLTP). Safety outcomes included assessment of treatment-emergent adverse events (TEAEs).A total of 96 patients (mean [SD] age, 54.4 [11.3] years; 52 female [54.2%]) entered the OLTP, of whom 88 (91.7%) completed the OLTP. Mean (SD) baseline LDL-C level was 145.9 (55.2) mg/dL. At week 72, evinacumab, 15 mg/kg, reduced mean (SD) LDL-C level from baseline by 45.5% (28.7%) in the overall cohort. Evinacumab, 15 mg/kg, reduced mean (SD) apolipoprotein B (38.0% [22.1%]), non-high density lipoprotein cholesterol (48.4% [23.2%]), total cholesterol (42.6% [17.5%]), and median (IQR) fasting triglyceride (57.2% [65.4%-44.4%]) levels at week 72 from baseline in the overall cohort. TEAEs occurred in 78 of 96 patients (81.3%). Serious TEAEs occurred in 9 of 96 patients (9.4%); all were considered unrelated to study treatment.In patients with refractory hypercholesterolemia, evinacumab provided sustained reductions in LDL-C level and was generally well tolerated.ClinicalTrials.gov Identifier: NCT03175367.
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Journal: JAMA Cardiology (2023)

Seung-Jun Lee, MD; Jung-Joon Cha, MD; Woong Gil Choi, MD; Wang-Soo Lee, MD; Jin-Ok Jeong, MD; Seonghoon Choi, MD; Yoon-Haeng Cho, MD; Woojung Park, MD; Chang-Hwan Yoon, MD; Yong-Joon Lee, MD; Sung-Jin Hong, MD; Chul-Min Ahn, MD; Byeong-Keuk Kim, MD; Young-Guk Ko, MD; Donghoon Choi, MD; Myeong-Ki Hong, MD; Yangsoo Jang, MD; Soon Jun Hong, MD; Jung-Sun Kim, MD; RACING Investigators; Kyeong Ho Yun; Bum-Kee Hong; Jung Ho Heo; Won Young Jang; Won-Yong Shin ; Sang Wook Im; Woong Chol Kang; Young Hoon Jung ; Yongwhi Park; Sung Yoon Lee; Seung Ho Hur; Hyun Hee Choi; Kyoung Jin Kim ; Ju Han Kim ; Hyun Kuk Kim ; Jung Hee Lee; Ung Kim ; Yu-Jung Choi ; Seung-Woon Rha; Yun-Hyeong Cho
Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2)
Authors: Roy M Fleischmann, Désirée van der Heijde, Vibeke Strand, Tatsuya Atsumi, Iain B McInnes, Tsutomu Takeuchi, Peter C Taylor, Marguerite Bracher, David Brooks, John Davies, Christopher Goode, Anubha Gupta, Sumanta Mukherjee, Ciara O’Shea, Didier Saurigny, Lorrie A Schifano, Celia Shelton, Julia E Smith, Millie Wang, Reena Wang, Sarah Watts, Michael E Weinblatt
Journal: Annals of the Rheumatic Diseases (2023)

To investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.